1. Field of the Invention
The present invention relates to a composition for curing Sjoegren syndrome diseases, comprising a derivative of spirooxathiolane-quinuclidine or an acid addition salt thereof as an active ingredient.
2. Description of the Background Art
Sjoegren syndrome, which is a xerotic disease caused by chronic inflammatory destruction of exocrine glands, occurs either independently or accompanied by various types of collagen diseases such as, for example, rheumatoid arthritis, systemic lupus erythematosus, progressive systemic sclerosis, polymyositis-dermatomyositis, or the like. It is an autoimmune disease which takes various pathologic forms. In addition, this disease is known to accompany lymphatic malignant tumors or quasi lymphomas at the final stage. Thus, this is a difficult-to-cure disease which attracts a great deal of attentions from medical experts. In Japan, the disease was designated as a specified disease (a difficult-to-cure disease) in 1976 by the Ministry of Health and Welfare. More recently, Tokyo metropolitan government also designated this disease as a specified disease (a difficult-to-cure disease). According to the survey made by a study team of the Ministry of Health and Welfare, the number of the patients of this disease was estimated to be 17,669 as of 1976. Nowadays, the patients is considered to have increased several times as many as in 1976, i.e., about 100,000. The disease is characterized by the fact that the number of female patients are predominant; above 90%, or the ratio of female and male patients being 38.8:1.
Irrespective of complications, the major clinical symptoms of Sjoegren syndrome are xerostomia, xerophthalmia, and xerotic keratoconjunctivitis.
There is no effective method of curing these symptoms. Symptomatic treatments, such as administration of artificial saliva, artificial tear, or respiratory tract secretion promoters, are practiced as main countermeasures. Steroidal drugs which are dosed for suppressing immune reactions are reported to be almost ineffective to these symptoms. In addition, they have unfavorable side effects. On the other hand, the systemic (e.g., oral or intravenous) administration of parasympathetic nerve (cholinergic) stimulants, conventionally known saliva and tear secretion accelerators, is gradually phasing out due to their extensive side effects. Even bethanechol, the only one cholinergic system stimulant currently used, cannot be used at all for the Sjoegren syndrome disease due to its comprehensive side effects such as headache, hot flush, palpitation, intrathoracic agony, nausea, emesis, diarrhea, abdominal discomfort, pyrosis, stomach discomfort, diaphoresis, and the like. Such a current medical situation gives the patients suffering from the Sjoegren syndrome disease conspicuous difficulty and inconvenience in carrying out the basic daily activities of living; eating, speaking, and seeing.
The object of the present invention is therefore to provide a drug for curing Sjoegren syndrome diseases which is safe and exhibits minimal toxicity as opposed to bethanechol which has extensive side effects.
In achieving this object, taking the advantage of the recent advancement in the research and development in parasympathetic nerve receptors, or cholinomimetic receptors, the inventors of the present invention synthesized and tested various chemical compounds possessing enhanced selectivity and specificity toward the central nervous system and the exocrine glands. As a result, the present inventors have discovered that derivatives of spirooxathiolane-quinuclidine, having the chemical structure of formula (I) shown below or their acid addition salts exhibit excellent effects.